Abstract
BackgroundCentral serous chorioretinopathy (CSC) is a severe and heterogeneous chorioretinal disorder. Shared clinical manifestations between CSC and age-related macular degeneration (AMD) and the confirmation of CFH as genetic risk locus for both CSC and AMD suggest possible common pathophysiologic mechanisms between two diseases.MethodsTo advance the understanding of genetic susceptibility of CSC and further investigate genetic pleiotropy between CSC and AMD, we performed genetic association analysis of 38 AMD-associated single nucleotide polymorphisms (SNPs) in a Chinese CSC cohort, consisting of 464 patients and 548 matched healthy controls.ResultsTwelve SNPs were found to be associated with CSC at nominal significance (p < 0.05), and four SNPs on chromosomes 1, 4, and 15 showed strong associations whose evidences surpassed Bonferroni (BF)-corrected significance [rs1410996, odds ratios (OR) = 1.47, p = 2.37 × 10–5; rs1329428, OR = 1.40, p = 3.32 × 10–4; rs4698775, OR = 1.45, p = 2.20 × 10–4; and rs2043085, OR = 1.44, p = 1.91 × 10–4]. While the genetic risk effects of rs1410996 and rs1329428 (within the well-established locus CFH) are correlated (due to high LD), rs4698775 on chromosome 4 and rs2043085 on chromosome 15 are novel risk loci for CSC. Polygenetic risk score (PRS) constructed by using three independent SNPs (rs1410996, rs4698775, and rs2043085) showed highly significant association with CSC (p = 2.10 × 10–7), with the top 10% of subjects with high PRS showing 6.39 times higher risk than the bottom 10% of subjects with lowest PRS. Three SNPs were also found to be associated with clinic manifestations of CSC patients. In addition, by comparing the genetic effects (ORs) of these 38 SNPs between CSC and AMD, our study revealed significant, but complex genetic pleiotropic effect between the two diseases.ConclusionBy discovering two novel genetic risk loci and revealing significant genetic pleiotropic effect between CSC and AMD, the current study has provided novel insights into the role of genetic composition in the pathogenesis of CSC.
Highlights
Central serous chorioretinopathy (CSC) is a common chorioretinal disorder characterized by serous sensorial retinal detachment (Balaratnasingam et al, 2016)
CSC patients cluster in families (Oosterhuis, 1996; Weenink et al, 2001), and the prevalence of CSC varies in different ethnic populations, with higher prevalence in Asians than in Caucasians and African Americans (Desai et al, 2003; How and Koh, 2006; Kitzmann et al, 2008; Tsai et al, 2013), suggesting that genetic compositions may contribute to the risk of CSC
We further investigated the impact of significantly associated risk variants on the clinical manifestations in CSC patients and compared the genetic effects of these loci between CSC and age-related macular degeneration (AMD)
Summary
Central serous chorioretinopathy (CSC) is a common chorioretinal disorder characterized by serous sensorial retinal detachment (Balaratnasingam et al, 2016) It is recognized as the fourth most incident eye disorder after age-related macular degeneration (AMD), diabetic retinopathy, and branch retinal vein occlusion among non-surgical retinopathies (Wang et al, 2008). Most of acute CSC patients have been described to be self-limiting, some patients still suffer recurrences or progress to a chronic condition, indicating interindividual variation of risk and clinical course in acute CSC. These clinical differences suggest that some aspects of underlying molecular pathogenesis might be different between acute and chronic CSCs. Central serous chorioretinopathy (CSC) is a severe and heterogeneous chorioretinal disorder. Shared clinical manifestations between CSC and age-related macular degeneration (AMD) and the confirmation of CFH as genetic risk locus for both CSC and AMD suggest possible common pathophysiologic mechanisms between two diseases
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